Combination effect of melatonin and dexamethasone on liver ischemia/reperfusion injury

Abstract

OBJECTIVE: Liver failure following ischemia-reperfusion (I/R) injury is a major concern in liver surgery. The purpose of this study was to evaluate combination pretreatment with melatonin (MEL) and dexamethasone (DEX) on liver I/R model. Male Wistar rats (n = 60) were assigned to 5 groups of 12 animals each: (1) Sham: laparotomy without I/R; (2) I/R: hepatic I/R; (3) I/R+MEL: hepatic I/R+rnelatonin injected intraperitoneally (20 mg/kg); (4) I/R+DEX: hepatic I/R+ dexamethasone injected intravenously (10 mg/kg); (5) I/R+MEL+DEX: hepatic I/R+ melatonin injected intraperitoneally+dexamethasone injected intravenously. The liver was subjected to ischemia by clamping the portal triad for 30 minutes and then reperfused for 6 hours after ischemia by removing the clamps. RESULTS: The levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) decreased after hepatic I/R in all groups. Levels of GPx and SOD were higher in I/R+MEL+DEX group compared to UR, I/R+MEL and I/R+DEX groups and they were significantly higher in I/R+MEL group compared to UR and I/R+DEX groups (p < 0.05). Levels of ALT, AST, TNF-alpha, hepatic tissue malondialdehyde (MDA), liver injury index, and apoptotic index increased after hepatic I/R. Levels of ALT, AST, tissue MDA, tissue injury index and apoptotic index were lower in I/R+MEL+DEX group compared to those in I/R, I/R+MEL and I/R+DEX groups, and in I/R+MEL they were significantly lower than in I/R+DEX group (p < 0.05). TNF-alpha level was lower in I/R+MEL+DEX group compared to other groups and it was significantly lower in I/R+DEX group than in I/R+MEL and I/R groups (p < 0.05). CONCLUSION: Combination therapy with melatonin and dexamethasone had better results in decreasing the liver injury compared to when each of them was administered alone (Tab. 3, Ref. 58). Text in PDF www.elis.sk.